Lean body weight‐adjusted intravenous iodinated contrast dose for abdominal CT in dogs reduces interpatient enhancement variability while providing diagnostic quality organ enhancement

Abstract Contrast‐enhanced computed tomography (CECT) is increasingly used to screen for abdominal pathology in dogs, and the contrast dose used is commonly calculated as a linear function of total body weight (TBW). Body fat is not metabolically active and contributes little to dispersing or diluting contrast medium (CM) in the blood. This prospective, analytic, cross‐section design pilot study aimed to establish the feasibility of intravenous CM dosed according to lean body weight (LBW) for abdominal CECT in dogs compared to TBW. We hypothesized that when dosing intravenous CM according to LBW, studies will remain at diagnostic quality, there will be a reduced interindividual contrast enhancement (CE) variability, and there will be less change to heart rate and blood pressure in dogs compared to when administering CM calculated on TBW. Twelve dogs had two CECT studies with contrast doses according to TBW and LBW at least 8 weeks apart. Interindividual organ and vessel CE variability, diagnostic quality of the studies, and changes in physiological status were compared between protocols. The LBW‐based protocol provided less variability in the CE of most organs and vessels (except the aorta). When dosed according to LBW, liver enhancement was positively associated with grams of iodine per kg TBW during the portal venous phase (P = 0.046). There was no significant difference in physiological parameters after CM administration between dosing protocols. Our conclusion is that a CM dose based on LBW for abdominal CECT lowers interindividual CE variability and is effective at maintaining studies of diagnostic quality.


INTRODUCTION
Contrast-enhanced computed tomography (CECT) is increasingly being used to investigate abdominal pathology in dogs, and the main technical parameter influencing solid visceral enhancement is the amount of iodine administered, with solid visceral enhancement increasing proportionally with iodine concentration. 1 The contrast medium (CM) dose is commonly adjusted according to the patient's total body weight (TBW), as it is simple to calculate and can be readily implemented to achieve adequate organ opacification. 2 However, CM dosage according to TBW fails to consider differences in body conformation, and because fat is poorly perfused and less metabolically active, TBW calculated regimens may lead to excessive contrast volume in overweight and obese patients. 3 Contrast enhancement (CE) during CT examination is affected by multiple factors related to the patient, CM, and CT scanning technique. 2 The important technique-related factors include CM volume, concentration, rate of injection, and type of injection. 4 In humans, key patient-related factors affecting CE are patient body size and cardiac output (cardiovascular circulation time), and among body size parameters, lean body weight (LBW) exhibits the strongest association with aortic and hepatic enhancement. 5 Excluding disease states that alter circulation, such as congestive heart failure, the most important patient-related factor is body weight. 4 The minimally sufficient iodine dose to achieve adequate parenchymal and vessel CE should be given to reduce any potential toxicity or adverse alteration to physiological functions. 2 In dogs, the empirically recommended dose for abdominal CT is 600 to 880 milligrams of iodine per kilogram (mgI/kg), which is higher than that for human adults (600 mgI/kg). 3, 6 Goic and coauthors found that contrast-induced kidney injury occurred in dogs administered a median contrast dose of 897.4 mgI/kg, just above the recommended dose range. 7 Acute severe reactions to intravenous contrast are rare, although moderate (>20% from baseline) bradycardia, tachycardia, hypotension, or hypertension when Iohexol was administered in 18.3% of anesthetized dogs have been reported. 8 Use of less iodinated contrast is particularly crucial in patients with preexisting renal dysfunction, dehydration, hypertension, or on nephrotoxic chemotherapeutic regimens; those patients have a higher risk of developing contrast-induced nephropathy (CIN) as CM is mainly excreted by the kidneys unmetabolized. 2,9 Lean body weight tailored contrast dosage has been studied in humans, as an obese patient has a high proportion of body fat and relatively small blood volume and extracellular compartment; the higher proportion of fat contributes little to dispersing or diluting CM in the blood. 2,10 It has been reported in people that LBW-adjusted contrast dose reduces patient-to-patient enhancement variability while maintaining satisfactory hepatic and vascular enhancement. 3,[11][12][13] In a recent study, a CECT protocol using 600 mgI/kg fat-free mass provided diagnostic liver enhancement and improved interpatient enhancement uniformity while reducing iodine dose. 14 Kondo 16 The positive association between aortic, hepatic, and portal enhancement was suspected to be due to a greater extracellular concentration of iodine in dogs with a higher abdominal fat percentage. 16 Findings from this study introduced evidence that abdominal fat percentage is significantly associated with organ attenuation values during abdominal CECT studies in dogs, and calculations for contrast dose may need to consider body fat as well as TBW.
The aim of the current study was to determine whether an LBW-adjusted contrast dose in CECT would have reduced interindividual enhancement variability, be of diagnostic quality, and produce fewer physiological changes in heart rate and blood pressure.
We hypothesized that, when dosing CM according to LBW, there would be reduced interpatient enhancement variability, satisfactory organ/vessel enhancement, and image quality, as well as lower changes to heart rate and blood pressure following CM administration.

CT study acquisition and LBW determination
All CT scans were performed with a 16-slice helical machine (Somatom x: abdominal fat volume in liters calculated by abdominal CT using the fat attenuation threshold range.
LBW was derived by subtracting the total DEXA fat mass from TBW, and all assessments and measurements were checked by J.K. Abdominal volume CT to calculate LBW as the method is shown to reliably estimate total body composition in dogs between 5.1-60 kg TBW as determined by DEXA. 20 The 12 dogs were administered 700 mgI/kg LBW through a cephalic vein catheter, with the same injection and acquisition protocol as the TBW-dosed CT scan.

Image analysis
Images

Demographic data
There were five female neutered and seven male neutered dogs. The study group consisted of a range of breeds, including two Boxers, two Staffordshire Bull Terriers, and eight other breeds. They had a median age of 7.5 years (range 1-13 years; interquartile range 5.0-9.5 years).
Descriptive statistics of the 12 dogs are summarized in Table 1

Organ enhancement
Box and whisker plots displaying data for CE of the aorta, liver, spleen, right kidney, and portal vein, comparing TBW to LBW dosing are shown in Figures 1 and 2.   (Figures 3 and 4).

Physiologic parameters
No significant difference was found when comparing heart rate, systolic blood pressure, and mean arterial pressure change after contrast administration between the two dosing methods ( Figure 5). TA B L E 2 Subjective evaluation of the quality of organ/vessel enhancement with intravenous contrast dosed according to TBW (n = 6) and LBW (n = 6) by two independent blinded radiologists Excellent: contrast enhancement provided optimal information to make a radiologic diagnosis. Good: contrast enhancement provided adequate information to make a radiologic diagnosis. Fair: contrast enhancement provided acceptable information to make a radiologic diagnosis, but image quality was unsatisfactory. Poor: contrast enhancement did not provide adequate information to make a radiologic diagnosis.

TA B L E 3
Linear regression analysis of relationships between organ/vessel contrast enhancement and iodine per kg TBW when contrast was dosed according to LBW

Coefficient of Determination (R 2 ) P-value
Arterial phase between TBW and LBW dosing protocols. 23,25 Two studies showed that the use of LBW (rather than TBW) resulted in a more precise estimation of iodine dose to achieve consistent hepatic enhancement with reduced patient-to-patient variability. 12,22 Zanca and coauthors also found that a fat-free mass-based protocol yielded similar findings and significantly reduced iodine load. 14 Based on reports in the human literature and findings from the present study, TBW may not be the optimal body size index for determining CM dose, particularly in obese patients with abundant body fat and thus relatively smaller vascular and interstitial spaces for their body weight. 3 In the present study, when dosed according to TBW, all the dogs had hepatic enhancement > 60 HU; this would equate to overenhancement in humans. 14 When contrast was dosed according to LBW, 5 of the 12 dogs in this study had hepatic enhancement < 50 HU, which is considered insufficient opacification in humans. 3,4,24 However, the enhancement was above 30 HU in all the dogs, which is the cut-off for inadequate enhancement in humans, when the conspicuity of lesions will be diminished. 26 In the study by Zanardo and co-workers, approximately half of the patients had a liver CE below 40 HU; however, they were considered diagnostic by radiologists. 25 This was thought to be due to technological improvements in both CT hardware and software that decreased not only the ionizing radiation dose but also the dose of CM needed for a diagnostic examination, and the authors suggested that the threshold of 50 HU for sufficient liver CE should be reconsidered. 25 In people, it was reported that approximately 0.5 g iodine per kg of TBW is required to achieve an average 50 HU increase in CE in the liver. 27 In the present study, this dose was only achieved in three of the 12 dogs when the dose was adjusted to LBW. This could explain why visual assessment of organ enhancement recorded fewer "excellent" scores in dogs dosed according to LBW. Interestingly, for both contrast dosing methods, splenic enhancement was generally lower, being scored as "fair" once when dosed according to TBW and four times when dosed according to LBW. The reason for this is not known; however, quantitative splenic enhancement with the fixed injection duration protocol was overall lower compared with a fixed portal phase acquisition timing in the study by Kan and coauthor. 16 This could be due to later performed portal studies when a fixed injection duration protocol is used. 18 Or reflect anatomic peculiarities for the spleen such as the splenic pulp.
In people, liver CE is considered the reference for solid organ parenchymal CE, and it is strongly influenced by CM biodistribution into the intra-and extravascular space but appears to be a nonlinear multiparametric function of several variables that may not be modeled by simply using TBW. 25 ing of CM may also prove beneficial for future studies relying on quantification of CE differences to classify disease types and presents an avenue for further investigation. The relationship between organ enhancement and CM dose seems to not be simply linear, however, with hidden compensating effects proposed in the human literature. 25 Future larger studies are needed to determine the ideal CM dose per LBW to achieve adequate liver enhancement in dogs while reducing the overall iodine load and achieving satisfactory image quality.

ACKNOWLEDGMENTS
The authors thank Anke Wiethoelter DrMedVet, MVPHMgt for the statistical help.